GABA Effects of Nicotine in Men and Women

描述（由申请人提供）：尼古丁已被证明影响大脑gaba能功能。在大鼠中，尼古丁会急剧增加GABA的释放，人类和动物研究表明GABA能系统与尼古丁成瘾的获得和维持有关。在初步的人体研究中，通过磁共振波谱（MRS）观察到尼古丁给药后人类皮层GABA水平的短暂增加。此外，尼古丁已被发现能将人脑中GABA的合成提高2-4倍。了解急性尼古丁给药对大脑GABA的影响，可能有助于了解吸烟与已知涉及GABA能系统的常见疾病（如抑郁症和酗酒）之间的相互作用。这个项目也可能提供关于为什么有些人很难戒烟的进一步信息。已有研究表明，与月经周期相关的大脑GABA水平变化被吸烟所消除，并且男性和女性对尼古丁的反应有所不同，因此本项目还将探索人类大脑中GABA能反应的性别差异。以下几个问题将得到解答：1)急性给药尼古丁是否会增加大脑GABA？2)大脑伽马氨基丁酸恢复到尼古丁摄入前的水平需要多长时间？3)尼古丁是否会增加GABA的合成？性别是否会影响尼古丁诱导的脑GABA水平和合成速率的变化？将测量40名健康吸烟者（20名男性，20名女性）一夜戒烟后大脑GABA的浓度和合成速率。测量将进行两次，一次使用尼古丁吸入器，一次使用安慰剂吸入器。排除标准将包括当前的神经精神疾病，或最近的病史。公共卫生相关性：这项工作将确定大脑皮层gaba能神经元的哪些变化与尼古丁和人们对尼古丁的一些主观感受有关。这些结果可能有助于解释为什么一些新的基于药物的戒烟方法是有效的，并指导新方法的发展。研究结果也有助于我们理解为什么抑郁症患者和酒精依赖患者更有可能对烟草上瘾。

DESCRIPTION (provided by applicant): Nicotine has been shown to affect GABAergic function in the brain. In rats, nicotine increases GABA release acutely, and human and animal studies have implicated the GABAergic system in the acquisition and maintenance of nicotine addiction. Transient increases in levels of human cortical GABA levels have been observed by magnetic resonance spectroscopy (MRS) with nicotine administration in preliminary studies in humans. Furthermore, nicotine has been seen to elevate brain GABA synthesis 2-4 fold in human brain. Knowing the effects of acute nicotine administration on brain GABA may provide insight into the interaction of tobacco smoking with prevalent disorders that are known to involve the GABAergic system, such as depression and alcoholism. This project may also provide further information about why it is so hard for some people to stop smoking. It has been shown that menstrual cycle related changes in brain GABA levels are abolished by smoking, and that men and women have some different responses to nicotine, so this project will also explore gender-based differences in GABAergic responses in the human brain. Several questions will be answered: 1) Does acute nicotine administration increase brain GABA? 2) How long does it take brain GABA to return to pre-nicotine levels? 3) Does nicotine increase GABA synthesis? 4) Does gender affect nicotine-induced changes in brain GABA levels and rates of synthesis? The concentration and rates of synthesis of brain GABA will be measured in 40 healthy smokers (20 men, 20 women) after overnight abstinence from smoking. The measurements will be conducted twice, once with a nicotine inhaler, and once with a placebo inhaler. Exclusion criteria will include current neuropsychiatric disorders, or a recent history of such. PUBLIC HEALTH RELEVANCE: This work will establish what changes in GABAergic neurons in the cerebral cortex are associated with nicotine and some of the subjective feelings that people experience with nicotine. The outcomes may help to explain why some of the newer drug-based smoking cessation approaches are effective and guide the development of new approaches. The results may also contribute to our understanding of why depressed people and patients with alcohol dependence have a greater likelihood of addiction to tobacco.